We wished to investigate the binding in vitro of adenovirus Type 5 to reconstituted rat brain microtubules because previous investigators had observed virus-microtubule associations inside infected cells. Our preliminary results strongly suggest that adenovirus binds specifically by hexon capsomeres to the high molecular weight components of the microtubules. Our observations support the hypothesis of Dales and Chardonnet (1973) that the transport of adenovirus within infected cells is mediated by an interaction with microtubules. We now intend to investigate in more detail the biological significance of the in vitro interaction using two approaches. First, we shall complete the identification of the interacting components of the virus and of the microtubule. Here the general approaches will be to investigate the interaction of virus and microtubules which lack certain components and to search for possible inhibitory effects of antibodies and of purified viral and microtubular proteins on the interaction. We shall develop quantitative methods by which we hope to measure the number and affinity of binding sites. We shall investigate the generality of the interaction in vitro using a series of adenoviruses and a series of microtubules (including microtubules from HeLa and KB cells, after we have developed the methods for isolation). Second, we shall perform quantitative morphometric investigations on the intracellular interaction of virus with microtubules during the early stages of infection. Here the objectives are to correlate the effects of various treatments which should increase or decrease the amount of microtubules in the cell with effects on virus-microtubule association and with effects on the course of infection by the virus. The effects of antibodies to virus and viral proteins will also be investigated. Tilting stage micrographs and stero pairs will be used to define the ultrastructural details of the interaction in situ.